Director's Report to the National Advisory Council on Drug Abuse

May, 2000

Research Findings

Research on AIDS and Other Medical Consequences of Drug Abuse

Obesity and Immune Function

Baum and her colleagues (Shor-Posner, et al.) report that mild to moderate obesity in HIV-infected chronic drug users does not impair immune function and is associated with better HIV-1-related survival. The investigators collected nutritional and immunological data, prior to protease inhibitor administration, in 125 HIV-1 seropositive participants (82 men and 43 women, mean age 42±6 years) and 148 HIV-1-seronegative controls from the Miami HIV-1-Infected Drug Abusers Study cohort at a community clinic from 1992 to 1996. Based on the body mass index (BMI) measurements, 18% of the HIV-1+ group was obese (BMI>27) in comparison to 29% of the seronegative group. Over an 18-month period, 60.5% of the non-obese HIV-1+ patients exhibited a 25% decline in CD4 cell count, compared with 18% of the obese patients (p < 0.004). During the follow-up period, 38% of the lean and 13% of the non-obese study subjects died of HIV-1 related causes. Measurements of BMI were inversely associated with progression to death, independent of CD4 cell count <200 cells/mm3 (p<0.02). These data suggest that mild-to moderate obesity in HIV-infected drug users has no significant effect on their immune function and is associated with better survival. Further research is underway to determine the long-term impact of obesity on disease progression in HIV-infected drug abusers. Shor-Posner, G., Campa, A., Zhang, G., Persaud, N., Maria-Jose Miguez-Burbano., and Baum, M. When Obesity Is Desirable: A Longitudinal Study of the Miami HIV-1-Infected Drug Abusers (MIDAS) Cohort. Journal of Acquired Immune Deficiency Syndrome, 23(1), pp. 81-88, 2000.

Elicitation Study Focuses on the Sexual Risk Practices of African American Crack Users

A descriptive elicitation research study was conducted in Washington, D.C. to better understand the attitudes, beliefs, and barriers that affect the adoption and maintenance of condom use to prevent sexual transmission of HIV. An ethnographer recruited 64 adults for participation in the study. Participants were interviewed using semi-structured interview guides that were developed as cognitive maps for interviewing, rather than as questionnaires. The data were coded and analyzed according to condom use outcome expectancies, normative beliefs about condom use, and contextual facilitators and barriers of condom use. Participants described few positive condom use outcome expectancies, while detailing several negative expectations. Participants described few contextual barriers to condom use, although situational barriers, including crack addiction, were identified. Unlike other studies, this project did not find that cultural or social factors inhibited women from introducing condoms into sexual relationships, other than those related to intimate sexual relationships or to the special situation of sex and crack. Culturally determined sexual scripts may be important in determining condom use: Normative beliefs were weakly related to condom use with casual partners, but strongly influenced condom use with intimate partners. Williams, M., Bowen, A., Elwood, W., McCoy, C., McCoy, V., et al. Determinants of Condom Use Among African Americans Who Smoke Crack Cocaine. Culture, Health, and Sexuality. 2(1), pp. 15-32, 2000.

Cocaine Regulation of the Chemokine and their Receptors

Chemokine receptors are important for the entry of human immunodeficiency virus (HIV) into most cells. Nair and his colleagues (SUNY at Buffalo) have shown an effect of cocaine on these chemokine systems. They have identified a cellular action for the known stimulation of HIV growth by cocaine. Earlier studies supported a significant role for cocaine in the susceptibility to and the progression of HIV-1 infection. Recently, several unique HIV-1 entry coreceptors (e.g., CCR5 and CCR3) and a trio of HIV-1-specific suppressor chemokines, namely, RANTES (regulated-upon-activation T expressed and secreted), macrophage inflammatory protein 1 alpha (MIP-1 alpha) and MIP-1 beta, were identified. Although cocaine has been linked to the immunopathogenesis of HIV-1 infection, the corresponding cellular and molecular mechanism(s) have not been well defined. We hypothesize that cocaine mediates these pathologic effects through the down-regulation of HIV-1-suppressing chemokines and/or up-regulating HIV-1 entry coreceptors in HIV-1-infected subjects, resulting in disease progression to AIDS. Our results show that cocaine selectively down-regulates endogenous MIP-1 beta secretion by normal peripheral blood mononuclear cells (PBMC), while cocaine did not affect the MIP-1 beta production by PBMC from AIDS patients. Cocaine also selectively suppresses lipopolysaccharide-induced MIP-1 beta production by PBMC from HIV-infected patients. Further, cocaine significantly down-regulates endogenous MIP-1 beta gene expression, while it up-regulates HIV-1 entry coreceptor CCR5 by normal PBMC, These studies suggests a role for cocaine as a cofactor in the pathogenesis of HIV infection and support the premise that cocaine increases susceptibility to and progression of HIV-1 infection by inhibiting the synthesis of HIV-I protective chemokines and/or up-regulating the HIV-1 entry coreceptor, CCR5. Nair, M.P.N., Chadha, K.C., Hewitt, R.G. Mahajan, S., Sweet, A. and Schwartz, S.A. Cocaine Differentially Modulates Chemokine Production by Mononuclear Cells from Normal Donors and Human Immunodeficiency Virus Type 1-Infected Patients. Clinical and Diagnostic Laboratory Immunology, 7(1), pp. 96-100, Jan 2000.

Gastrointestinal Infections and Opiates

Patients infected with HIV suffer from increased incidence and severity of a number of opportunistic infections of the gastrointestinal tract, including Salmonella typhimurium, and others such as cryptosporidium. The present studies showing that MU opioid agonists increase susceptibility to oral infection with Salmonella suggest that use of heroin type drugs may be a cofactor in increased incidence of infection with this organism in HIV infected patients. The studies showing that morphine inhibits intestinal IgA and IgG antibody responses to a microbial toxin could provide a mechanism to account for these chronic gastrointestinal infections and the enhanced severity of these infections in HIV infected individuals who abuse opioids. To assess whether morphine potentiated Salmonella replication, a strain of Salmonella containing a temperature sensitive plasmid, was used. These grow at the permissive temperature of 30'C, but not at 37'C, that is, in the body. When the organisms are inoculated orally into mice, the plasmid in the Salmonella cannot replicate. Thus, when the bacteria are recultured from inoculated animal tissue using agar, with and without antibiotic, the number of plasmid--free (antibiotic sensitive) and plasmid-bearing (antibiotic resistant) bacteria can be enumerated. It was found that >95% of the organisms retrieved from the morphine--treated mice were plasmid-free, whereas in the original inoculum approximately 80% of the organisms contained the plasmid. These results show that in the morphine-treated mouse the wild type Salmonella replicated vigorously in the gastrointestinal tract, producing plasmid-free progeny, and that morphine potentiates Salmonella replication. In contrast, the other types of opiates, U50,488H (kappa), DPDPE (delta-1), or deltorphin (delta-2) produced no detectable Salmonella in any of the tissues. These results suggest that a predominantly mu agonist (morphine) has a greater effect than the delta1, delta2 or k agonists in potentiating gastrointestinal opportunistic infections such as Salmonella. MacFarlane, A.S., Peng, X., Meissler, J.J. Jr., Rogers, T.J., Geller, E.B., Adler, M. W. and Eisenstein, T.K. Morphine Increases Susceptibility to Oral Salmonella typhimurium Infection. J. Infect. Dis., 181(4), pp. 1350-1358, April 2000.

Perceptions of Tuberculosis and Treatment Adherence for Adolescents and Adults with HIV

HIV-infected individuals are a population at very high risk for and often among the least able to afford health care resources. In this study of adolescents and adults infected with HIV, interviews were completed to assess perceptions of tuberculosis (TB) infection rates and physician TB behavior, and patient knowledge of TB transmission and treatment adherence. The sample consisted of HIV-infected youth (N = 199) from adolescent clinical care sites in three cities and HIV-infected adults (N = 133) in New York. Adolescents reported they were significantly less likely to be tested for TB; however, testing rates were high for both samples. Results indicated that approximately 9% of both samples reported infection with TB; the majority reported receiving medication (97%), and consistent medication adherence (93%). The overall mean knowledge score regarding TB was 66% and there were significant age differences, with adolescents less knowledgeable than adults, and young males tending to be less knowledgeable than young females. Age, gender and experience with TB (self-perception of TB, testing history and clinic choice) significantly predicted accuracy of knowledge about TB. Results suggest that education and support from their community health care sources may substantially reduce chances of contracting and spreading TB. Murphy, D.A., Rotheram-Borus, M.J., and Joshi, V. HIV-Infected Adolescent and Adult Perceptions of Tuberculosis Testing, Knowledge and Medication Adherence in the USA. AIDS Care-Psychological and Socio-Medical Aspects of AIDS/HIV, 12(1), pp. 59-63, 2000.

Amphetamine Use in Youths Living with HIV (YLH)

In this study amphetamine use and its correlates were examined among 337 youths living with HIV (YLH) to determine whether its use is associated with increased transmission acts and poor health. One third of YLH engaged in amphetamine use in their lifetime, and 21% reported current use (last 3 months). Results showed that compared with those who never used (never-users), users initiated other drug use at younger ages, used more types of drugs, reported more emotional distress, employed escape coping significantly more frequently, had more sexual partners and more sexual encounters. Although users and never-users did not differ on physical symptoms or whether they have been diagnosed with AIDS, users reported significantly higher T-cell counts than never-users. Despite poor psychosocial functioning, amphetamine users have higher T-cell counts than other YLH. The continued high-risk profile of transmission acts among users suggests that preventive interventions must target specific drugs used by YLH. Rotheram-Borus, M.J., Mann, T., and Chabon, B. Amphetamine Use and Its Correlates Among Youths Living with HIV. AIDS Education and Prevention, 11(3), pp. 232-242, 1999.

Correlates of Perceived Compliance with AZT Dosing Among African American Drug Users

A pilot study was conducted in Washington, DC, to explore the associations between sociodemographic, drug use, and health belief factors and perceived compliance with zidovudine (AZT). The sample for this data analysis focused on 47 African American current drug injectors or crack cocaine smokers who were also HIV seropositive and receiving treatment for HIV infection. Participants were interviewed using a questionnaire developed for the study. Compliance was measured as perceived compliance; perception of compliance was measured by asking how often participants believed that they missed taking a specified medication, using a 5-point, Likert-type scale. The analyses demonstrated that HIV positive drug users are not a homogenous group in terms of compliance. Approximately a third of the drug users perceived that they were always compliant with AZT dosing and by implication, with other medications, including protease inhibitors. Perceived compliance was found negatively correlated with age, homelessness, number of injections in the previous 30 days, trading sex for drugs, and the perception that AIDS is no longer a serious disease since the development of new antiretroviral medications. Intensity of feelings of joy, fear, and the belief that taking more anti-HIV medications would result in better health were found to be positively correlated. Stability of lifestyle is an important factor in determining the level of compliance with HIV antiretroviral drugs, suggesting that factors associated with a stable lifestyle (not being homeless, trading sex for drugs, or injecting drugs, and having more social resources and peer and social supports) are key for interventions aimed at increasing compliance with antiretroviral medications among racial/ethnic minority drug users receiving treatment for HIV infection. Williams, M., Bowen, A., Ross, M., Freeman, R., and Elwood, W. Perceived Compliance with AZT Dosing Among a Sample of African-American Drug Users. International J. STD and AIDS, 11, pp. 57-63, 2000.

Patterns of Methamphetamine Use Among High Risk Men Are Complex and Variable

An ethnographic study was conducted in the Pacific Northwest to characterize the patterns of methamphetamine use among high risk men who use drugs and have sex with men (DUMSM). Data collection involved contextual, unobtrusive community observations; focus group interviews with service providers and community leaders; and semi-structured interviews with 103 men who currently used methamphetamine. Most of the men identified themselves as gay; and 20% were non-White (Native American, Latino, African American), reflecting the ethnic/racial background of the Seattle King County AIDS caseload. Almost all of the sample were HIV positive or had an AIDS diagnosis. The data indicate that there are complex and possibly overlapping social and cultural ecologies among injection drug-using men who have sex with men in the Seattle area. Most of the participants reported extensive histories of intermittent or ongoing drug use, including cocaine, MDMA (ecstasy), marijuana, heroin, and alcohol. All reported that, when they tried methamphetamine, they became "hooked." In fact, some participants said it was easier to stop using heroin than methamphetamine. Nearly half of the interviewees reported injection as their primary method of drug use. Study participants reported widely variable strategies for having safer sex in their intimate encounters, with some saying they used condoms more with casual partners than with intimate partners. Many of the participants reported that they were less likely to discuss their HIV status with potential sex partners if they were high on methamphetamine. Gorman, E.M. and Carroll, R.T. Substance Abuse and HIV: Considerations with Regard to Methamphetamine and Other Recreational Drugs for Nursing Practice and Research. J Assoc. Nurses in AIDS Care, 11(2), pp. 51-62, 2000.

Determinants of the Quantity of Hepatitis C Virus RNA

The quantity of hepatitis C virus (HCV) RNA was assessed in 969 persons who acquired HCV through injection drug use. Serum HCV RNA levels covered the linear range of the assay (from 200,000 to >120million equivalents/mL). The mean log10 HCV RNA level was significantly higher in 468 HIV-infected IDUs vs. 501 HIV-uninfected IDUs (P<.001). Among the HIV-uninfected IDUs, lower HCV RNA was independently associated with younger age (P<.001), ongoing hepatitis B infection (P=.005), and the absence of needle sharing (P=.020). However, more than 90% of the variability of HCV RNA levels was not explained by these sociodemographic, environmental and virologic factors, indicating the need for further research to determine what factors are responsible for the level of HCV RNA in the blood. Thomas, D.L., Astemborski, J., Vlahov, D., et al., JID, 181, pp. 844-851, 2000.

A Prospective Study of HIV Disease Progression in Female and Male Drug Users

Disease progression and mortality was assessed in a cohort of drug users attending a methadone maintenance program with on-site primary care. CD4 cell decline and distribution of AIDS-defining illnesses were studied in a cohort of 222 HIV-infected women and 302 HIV-infected men. Rates of CD4 cell decline, the distribution of first AIDS-defining illnesses, and the time to clinical AIDS did not differ by sex. Mortality rates for women and men were similar (8.71/100 person yrs. vs. 9.85/100 person yrs). However, CD4 cell count, two or more HIV-related symptoms, and crack-cocaine use were associated with an AIDS outcome. Webber, M.P., Schoenbaum, E.E., Gourevitch, M.N. et al., AIDS, 13, pp. 257-262, 1999.

Researchers examined the nature of the HIV/AIDS epidemic among marginalized drug users in Rio de Janeiro, with a specific focus on differential infection rates in economically distinct communities. Indigenous outreach workers recruited 1,544 cocaine users from a variety of "shantytown" and rural target areas or favelos that are clustered on the hills and mountainsides of Rio and from "asphalt" areas or districts of the city that contain basic infrastructure (i.e., downtown and residential areas). Researchers found that the HIV infection was introduced early into the upper and middle classes of Rio, but now appears to be penetrating into younger, more impoverished, and more rural populations concurrently with the rise in injection drug-related and heterosexually acquired cases of AIDS. They point out that, as the epidemiology of HIV changes, increasing numbers of people who were not targets of early information and prevention campaigns are at significant risk of infection. The findings indicate that it is feasible to access impoverished communities using indigenous outreach workers, and that residents of impoverished areas are willing to participate in AIDS education/prevention programs. The lower HIV prevalence in the impoverished communities in Rio appears to be a function of two factors: (1) the initial introduction of HIV to Brazil seems to have occurred primarily in upper and middle classes, and (2) even though favela residents have high risks for HIV, their social networks are isolated and excluded from the mainstream. The isolation may have been somewhat protective up to now, but with the infection beginning to appear among younger, high risk, impoverished, and rural populations at this time, the need is urgent for a renewed HIV information and prevention campaign-one that targets highly marginalized persons not reached when the campaigns were initially launched. Surratt, H., Indigence, Marginalization, and HIV Infection Among Brazilian Cocaine Users. Drug and Alcohol Dependence, 58, pp. 267-274, 2000.

Hepatitis B Infection among Young Injection Drug Users

This study compares the demographic characteristics and risk behaviors for hepatitis B infection among injection drug users younger than 30 years with those aged 30 or older to evaluate participants' knowledge, attitudes, and experiences of infection, screening, and vaccination against hepatitis B virus. A systematic sample of injection drug users not currently in a treatment program were recruited and interviewed at needle exchange programs and community sites. Participants were 135 injection drug users younger than 30 years and 96 injection drug users aged 30 or older. Injection drug users younger than 30 were found to be twice as likely as drug users aged 30 or older to report having shared needles in the past 30 days (36/135 [27%] vs 12/96 [13%]). Injection drug users younger than 30 were also twice as likely to report having had more than two sexual partners in the past 6 months (80/135 [53%] vs 29/96 [30%]). Although 88 of 135 (68%) young injection drug users reported having had contact with medical providers within the past 6 months, only 13 of 135 (10%) had completed the hepatitis B vaccine series and only 16 of (13%) perceived themselves as being at high risk of becoming infected with the virus. The authors concluded that young injection drug users have been immunized even though they have more frequent contact with medical providers and are at a higher risk for new hepatitis B infection than older drug users. Clinicians caring for young injection drug users and others at high risk of infection should provide education, screening, and vaccination to reduce an important source of hepatitis B infection. Seal, K.H., Edlin, B.R., Ochoa, K.C., Tulsky, J.P., Moss, A.R., Hahn, J.A. Risk of Hepatitis B Infection among Young Injection Drug Users in San Francisco: Opportunities for Intervention. Western Journal of Medicine, 172(1), pp. 16-20, 2000.